Growing evidence indicates that retinoic acid (RA), an oxidized derivative of vitamin A (VA), is required for cells to commit to a neuronal phenotype. Nuclear retinoic acid receptors (RARs) and enzymes with the capacity to synthesize RA persist in terminally differentiated neural tissues such as adult eye and brain. Relatively high levels of retinoids have been measured in adult neural retina, cochlea and organ of corti. Thus, it is likely that RA is functional in mature neuronal cells, perhaps influencing them to maintain their terminally-differentiated state. The principal investigator (PI) proposes to test the following hypotheses: (1) VA status effects the differentiation and/or maturation of olfactory neurons, and (2) VA status has differential effects on gene expression patterns in regenerative (olfactory epithelium) and terminally-differentiated (retina), adult neuronal tissues. The results of the proposed studies will contribute to our fundamental understanding of processes that control normal neuronal development and function and will provide a basis for determining the mechanisms that underlie pathologies associated with neurodegenerative diseases. CANDIDATE. The PI is a newly independent scientist who is funded by an NIH/MBRS Research Award. She is requesting salary support to release her from teaching and University service responsibilities so that she can become a productive researcher. This would allow her to devote at least 85 percent of her professional effort to accomplishing her research objectives (graded: 100 percent in year 1 to 85 percent in year 5). ENVIRONMENT. Tennessee State University (TSU) and the Department of Biological Sciences are supportive of the candidate's research career goals because of their current focus on building a strong, recognized, research program that supports the recently approved Ph.D. program in Biomedical Sciences. The candidate is a member of a Neuroscience Research Core Group at TSU that is composed of seven faculty researchers whose interests encompass Biochemistry, Physiology, Pharmacology, and Developmental, Cell and Molecular Biology. The candidate has an active collaboration an ongoing interactions with researchers at the neighboring campuses of Vanderbilt University and Meharry Medical College. A contractual agreement between TSU and Vanderbilt University assures compliance with Public Health Service Policy on the humane care and use of the vertebrate animals used the PI's research project. RESEARCH GOALS. The PI's research goals are to develop a neuronal model system to answer basic questions regarding the function of retinoids in neural systems, including the means by which RA is synthesized (what are the phsyiologically-relevant enzymes), transported (is RA made locally), and used (does RA directly or indirectly affect neurogenesis in vivo). The PI is committed to a career in biomedical research with a focus on chemosensory systems. With this award, the PI can increase her independent research capability and become competitive for NIV R01-level funding.